G-protein signaling TC21 regulation pathway
TC21 regulation pathway Related RAS viral (r-ras) oncogene homolog 2 ( TC21 ) belongs to Ras family ofsmall GTPases. It plays pivotal role in cell growth and differentiation ,. Guanine nucleotide exchange factors (GEFs), which promote GTP loading on TC21are essential for TC21 activation and GTPase activating proteins (GAPs), whichstimulate hydrolysis of GTP to GDP, negatively regulates TC21 activity . Main GEFs for TC21 are RAS guanyl releasing proteins 1, 2 and 3 (CALDAG-GEFII, CALDAG-GEFI, CALDAG-GEFIII ) that can be activatedby increased Ca(2'+) cytosol and DAG levels , ; Ras protein-specific guanine nucleotide-releasing factor 1 ( RASGRF1 )that is activated by Lymphocyte-specific protein tyrosine kinase ( Lck )phosphorylation , , ; and Rap guaninenucleotide exchange factor (GEF) 1 ( C3G ) that is stimulated by Growth factorreceptor-bound protein 2 ( GRB2 ) binding , . Known GEF for TC21 is RAS p21 protein activator 1 ( p120GAP ) , . Breakpoint cluster region ( BCR ) via Docking protein1 and 2 ( DOK1, DOK2 ) phosphorylation stimulates GAP activity ofp120GAP , . V-src sarcoma ( c-Src )phosphorylation and RAP1A, member of RAS oncogene family ( RAP-1A ) bindingsuppress GAP activity of p120GAP , . RAS p21protein activator 2 ( RASA2 ), activated by Inositol 1,3,4,5-tetrakisphosphatecytosol binding or G-protein alpha-12 family signaling, also exhibits GAPactivity towards TC21 , , . Anotherknown TC21 GAP is Neurofibromin 1 ( Neurofibromin ) ,. GTP-bound TC21 can stimulate the Raf kinase family members v-raf-1 murineleukemia viral oncogene homolog 1 ( c-Raf-1) and v-raf murine sarcoma viraloncogene homolog B1 (B-raf) and thus promote activation of Mitogen-activatedprotein kinases 1 and 3 ( Erk(MAPK1/3) ) , .